The mammalian egg responds to fertilization with a dramatic activation of physiological processes. Ion channels open, causing the membrane potential to change. Cortical granules undergo exocytosis resulting in modification of the egg membrane and extracellular coats, and establishing a block to polyspermy. Meiosis, arrested at second metaphase, resumes, and the egg prepares for cell division and further development. Over the last several years, evidence has been obtained, based on studies of sea urchin and frog, that activation of the egg may be initiated by a sequence of events involving guanine nucleotide binding proteins, metabolism of inositol lipids, and release of intracellular calcium. The objective of this research is to examine the initial steps which couple sperm-egg contact to the activation of development in the mammalian egg. Particular emphasis will be on study of the initiation of cortical granule exocytosis. In mammals, exocytosis of cortical granules results in modification of the extracellular coats of the egg which prevents polyspermy. Exocytosis could also be involved in the plasma membrane block to polyspermy that occurs in some species. An understanding of the mechanism responsible for exocytosis gained from these studies will be valuable for others studying polyspermy preventing mechanisms. One specific aim of this study of fertilization in the mouse egg is to determine the timing and calcium-dependence of cortical granule exocytosis. Another aim is to test the hypothesis that a guanine nucleotide binding protein is responsible for activation. The cellular messengers that might be responsible for conducting the signal for activation include inositol triphosphate, diacylglycerol and calcium; the other aims of this study are to determine the role of these substances in activation of the egg. It is important to examine these mechanisms in a mammalian egg where the events of fertilization are certainly more similar to those occurring in the human egg. The research may have implications for study of human reproduction and this basic research may find applications to problems in human fertility, infertility, contraception, and occurrence of polyspermy.